The eukaryotic proteins of the SWEET family are found in plants, animals, protozoans, bacteria, etc. They have 7 TMSs in a 3+1+3 repeat arrangement. These proteins appear to catalyze facilitated diffusion (entry or export) of sugars across the plant plasma membrane or the endoplasmic reticulum membrane (Takanaga and Frommer, 2010). Plant sweets fall into four subclades (Chen et al., 2010). The tomato genome encodes 29 SWEETs. Feng et al. 2015 analyzed the structures, conserved domains, and phylogenetic relationships of these proteins, and also analyzed the transcript levels of SWEET genes in various tissues, organs, and developmental stages in response to exogenous sugar and adverse environmental stress (e.g., high and low temperatures). The phylogeny of SWEETS has been described (Jia et al. 2017). A database (dbSWEET) of SWEET homologues is freely available to the scientific community at http://bioinfo.iitk.ac.in/bioinfo/dbSWEET/Home (Gupta and Sankararamakrishnan 2018). SWEETs perform diverse physiological functions in plants such as pollen nutrition, nectar secretion, seed filling, phloem loading, and pathogen nutrition (Jeena et al. 2019). Various SWEETS transport various sugars such as sucrose, fructose, glucose, galactose, and mannose (Hu et al. 2019). SWEETS play important roles in sugar efflux, pollen nutrition, nectar secretion, phloem transport, and seed development (Cao et al. 2019). Identification and expression analysis of the SWEET gene family from Poa pratensis under abiotic Stresses has been published (Zhang et al. 2020). The role of SWEET proteins in fruit development and abiotic stress in pomegranate (Punica granatum) has been reviewed (Kumawat et al. 2022). Garlic (Allium sativum L.) has 27 genes encoding clade I-IV SWEET proteins. The promoters of these genes contained hormone- and stress-sensitive elements associated with plant response to phytopathogens (Filyushin et al. 2023). The HuSWEET Family in Pitaya (Hylocereus undatus) has been identified, and key roles of HuSWEET12a and HuSWEET13d in sugar accumulation have been established (Jiang et al. 2023). Genome-wide identification and expression analysis of the SWEET gene family in annual alfalfa (Medicago polymorpha) has been achieved (Liu et al. 2023).
On average, angiosperm genomes contain approximately 20 SWEET paralogs, most of which serve distinct physiological roles. In Arabidopsis, AtSWEET8 and 13 feed the pollen; SWEET 11 and 12 provide sucrose to MFS-type sucrose transporters for phloem loading; AtSWEET11, 12 and 15 have distinct roles in seed filling; AtSWEET16 and 17 are vacuolar hexose transporters; and SWEET9 is essential for nectar secretion (Eom et al. 2015). The remaining family members await characterization, and could play roles in the gametophyte and elsewhere in the plant. In rice and cassava, and possibly other systems, sucrose transporting SWEETs play central roles in pathogen resistance. Plant sweets participate in diverse physiological processes, including pathogen nutrition, seed filling, nectar secretion, and phloem loading. There are 28 SWEET genes in tea (Camellia sinensis), and several members from the CsSWEET gene family have been localized and characterized (Jiang et al. 2021). Members of this family have been reported to have the MtN3 fold (Ferrada and Superti-Furga 2022). AtSWEET11 and AtSWEET12 transporters function in tandem to modulate sugar flux in plants (Fatima et al. 2023). SWEET proteins are involved in sugar efflux, phloem loading, reproductive development, plant senescence, and stress responses. There are 23 SWEET transporter encoded within the Medicago polymorpha (alfalfa) genome (Liu et al. 2023), and the transcriptional regulation of several have been determined.
Plant SWEETs play crucial roles in cellular sugar efflux processes: phloem loading, pollen nutrition and nectar secretion. Bacterial SemiSWEETs often consist of a triple-helix bundle and form semi-symmetrical, parallel dimers, thereby generating the translocation pathway. Two SemiSWEET isoforms have been crystallized, one in an apparently open state and one in an occluded state, indicating that SemiSWEETs and SWEETs are transporters that undergo rocking-type movements during the transport cycle (Xu et al., 2014). In SemiSWEETs and SWEETs, two triple-helix bundles are arranged in a parallel configuration to produce the 6- and (3 + 1 + 3) -transmembrane-helix pores, respectively. Given the similarity of SemiSWEETs and SWEETs to PQ-loop amino acid transporters and to mitochondrial pyruvate carriers (MPCs), the structures characterized by Xu et al., 2014 may also be relevant to other transporters in the TOG superfamily (Yee et al. 2013). Characterization and expression profiling of the 30 SWEET proteins (8 with one repeat unit, 21 with two, and 1 with 4) in cabbage (Brassica oleracea) revealed their roles in chilling and clubroot disease responses.
Latorraca et al. 2017; captured the translocationprocess by crystallography and unguided molecular dynamics simulations, providing an atomic-level description of alternating access transport. Simulations of a SWEET-family transporter initiated from an outward-open, glucose-bound structure spontaneously adopts occluded and inward-open conformations matching crystal structures. Mutagenesis experiments validated simulation predictions suggesting that state transitions are driven by favorable interactions formed upon closure of extracellular and intracellular 'gates' and by an unfavorable transmembrane helix configuration when both gates are closed. This mechanism leads to tight allosteric coupling between gates, preventing them from opening simultaneously. The substrate appears to take a 'free ride' across the membrane without causing major structural rearrangements in the transporter.
Plant SWEET sugar transporters play roles in phloem transport, nectar secretion, pollen nutrition, stress tolerance, and plant-pathogen interactions (Gao et al. 2017). Fify nine family members have been identified in wheat. Phylogenetic relationships, numbers of TMSs, gene structures, and motifs showed that TaSWEETs have 3-7 TMSs fall into four clades with 10 different types of motifs. Examination of the expression patterns of 18 SWEET genes revealed that a few are tissue-specific while most are ubiquitously expressed. Using a stem rust-susceptible cultivar, 'Little Club' (LC) the expression of five SWEETs tested induced following inoculation (Gao et al. 2017). Sugar is transported via SWEETS and semi-SWEETS from the extracellular side (via an outward-open state) to the intracellular side (inward-open state) through an intermediate occluded state with both extracellular and intracellular gates closed (Bera and Klauda 2018).
SWEET transporters play roles in phloem loading, seed and fruit development, pollen development, and stress response in plants. Longan (Dimocarpus longan), a subtropic fruit tree with high economic value, is sensitive to cold. A total of 20 longan SWEET (DlSWEET) genes were identified, and their phylogenetic relationships, gene structures, cis-acting elements, and tissue-specific expression patterns were systematically analyzed (Fang et al. 2022). This family is divided into four clades. Gene structure and motif analyses indicated that the majority of DlSWEETs in each clade share similar exon-intron organization and conserved motifs. Tissue-specific gene expression suggested diverse possible functions for DlSWEET genes. DlSWEET1 responds to cold stress, and the overexpression of DlSWEET1 improved cold tolerance in transgenic Arabidopsis, suggesting that DlSWEET1 might play a positive role in D. longan's responses to cold stress (Fang et al. 2022).
Alfalfa Nodulin MtN3
MtN3 of Medicago truncatula (P93332)
Golgi/E.R. Sweet1 glucose/galactose facilitator (Km ≥ 50mM) (Chen et al. 2010)
Sweet1 of Caenorhabditis elegans (O45102)
The sea squirt sugar transporter, Rga or Sweet1; required for normal development (Hamada et al., 2007; Chen et al., 2010).
Rga of Ciona intestinalis (F6U696)
Slv of Drosophila melanogaster
Bidirectional sugar (sucrose) transporter SWEET11 (AtSWEET11). Oligomerization, probably to the dimeric form, has been demonstrated (Xuan et al. 2013). Important for phloem loading.
SWEET11 of Arabidopsis thaliana
SWEET homologue of 375 aas and 7 TMSs in a 3 + 4 arrangement.
Stramenopiles (Marine diatom)
SWEET homologue of Phaeodactylum tricornutum
Uncharacterized protein of 262 aas and 7 TMSs
UP of Galdieria sulphuraria (Red alga)
MtN3-like protein of 686 aas and 7-8 TMSs, 1 N-terminal and 7 between residues 380 and 590.
MtN3-like protein of Plasmodium falciparum
SWEET2b sugar transporter. Sequesters sugars in root vacuoles. The 3-d structure is known. The subunit consists of two asymetic triple helix bundles (TMSs 1-3 and 5-7) connected by TMS4. SWEET2b is in an apparent inward (cytosolic) open state forming homomeric trimers. TMS4 tightly interacts with the first triple-helix bundle within a protomer and mediates key contacts among protomers (Tao et al. 2015).
SWEET2b of Oryza sativa
Sweet1 (SLC50A1). 99.6% identical to the goat (Capra hircus) mammary gland epithelial homologue which has been characterized (Zhu et al. 2015).
Sweet1 of Ovis aries (sheep)
Sweet family member of 305 aas and 7 TMSs. Mediates both low-affinity uptake and efflux of sugars across the membrane. (Wu et al., 2008)
Sweet of Citrus clementina
Uncharacterized protein of 197 aas and 7 TMSs
UP of Acidimicrobium sp. BACL27
Uncharacterized duplicated protein of 709 aas and 15 TMSs in a 7 + 7 + 1 arrangement. The protein contains two 7 TMS Sweet domains followed by an Atrophin-1 domain. There is no close homologue in the NCBI database, suggesting that it could be a result of a sequencing artifact.
UP of Ananas comosus
Uncharacterized protein of 1089 aas and 28 TMSs in a 7 + 7 + 7 + 7 arrangement.
UP of Phytophthora ramorum (Sudden oak death agent)
Vacuolar hexose (fructose) transporter of 230 aas and 7 TMSs, Sweet16 (Eom et al. 2015). It plays an iimportant role in cold tolerance (Wang et al. 2018).
Sweet16 of Arabidopsis thaliana (Mouse-ear cress)
Sweet9 of 258 aas and 7 TMSs. Important for nectar secretion (Eom et al. 2015).
Sweet9 of Arabidopsis thaliana (Mouse-ear cress)
Sweet family member of 89 aas and 3 TMSs. Associated with a trehalose phosphatase, possibly suggesting al role in trehalose transport.
Semi-sweet of Methanobacterium lacus
Sweet13 (Sweet12) of 294 aas and 7 TMSs. Transports the plant hormone, gibberellin (GA). Sweet14 also transports gibberellin. A double mutant has a defect in anther dehiscence. This mutant also exhibits altered long distant transport of exogenously applied GA and altered responses to GA during germination and seedling stages (Kanno et al. 2016). In dragon fruit (pitaya; H. undatus) Sweets function in phloem loading, seed filling, nectar secretion, and fruit sweetness development (Jiang et al. 2023).
SWEET13 of Arabidopsis thaliana (Mouse-ear cress)
SWEET transporter 1 of 262 aas and 7 TMSs. Plays a role in the D. officinale symbiotic germination process (Zhang et al. 2016). This organism provides a traditional chinese medicine. There are 25 SWEET genes in this organism (Hao et al. 2023). Most have 7 TMSs and contain two conserved MtN3/saliva domains. They were divided into four clades, and are found in various tissues. Sixteen were significantly regulated under cold, drought, and MeJA treatment (Hao et al. 2023).
Sweet transporter of Dendrobium officinale
Bidirectional sugar transporter, SWEET2a, of 2243 aas and 7 TMSs. It mediates both low-affinity uptake and efflux of sugars across the plasma membrane and plays a role in early seed development in Litchi chinensis (Xie et al. 2019).
SWEET2a of Oryza sativa subsp. japonica (Rice)
Bidirectional sugar transporter SWEET3b of 2252 aas and 7 TMSs. It mediates both low-affinity uptake and efflux of sugars across the plasma membrane and plays a role in early seed development in Litchi chinensis (Xie et al. 2019).
SWEET3b of Oryza sativa subsp. japonica (Rice)
Senescence-associated protein 29, SAG29 (SWEET15)
SAG29 of Arabidopsis thaliana (Q9FY94)
Bidirectional sugar transporter SWEET7, of 258 aas and 7 TMSs. It mediates both low-affinity uptake and efflux of sugar across the plasma membrane. AtSWEET7 transports glucose and xylose simultaneously with no inhibition (Kuanyshev et al. 2021).
SWEET7 of Arabidopsis thaliana (Mouse-ear cress)
Stromal cell protein (SCP) homologue, HsSWEET1 or RAG1AP1. Transports glucose and galactose bidirectionally. Present in the ER, Golgi and plasma membrane (Chen et al., 2010).
SLC50A1 of Homo sapiens
Ruptured pollen Grain-1, Sweet8 or Nodulin MtN3 family protein (essential for pollen viability). (Guan et al., 2008; Chen et al. 2010).
RPGI of Arabidoposis thaliana (Q8LFH5)
Host disease susceptible protein, Xa13 or Os8N3, for bacterial blight (Yang et al., 2006; Chu et al., 2006). Bidirectional sugar transporter, Sweet 11 (Chen et al., 2010)
Oryza sativa (Q6YZF3)
Nec1; predominantly expressed in nectaries; involved in sugar metabolism and nectar secretion (Ge et al., 2000)
Nec1 of Petunia hybrida (Q9FPN0)
Rga (Recombination-activating gene 1) (Hamada et al., 2005)
Rga of Mus musculus (Q9CXK4)
Sweet1: bidirectional low affinity glucose uniporter, Km = ~9 mM (Does not transport mannose, fructose or galactose) (Chen et al. 2010). The structure is know, and three regions, each containing several well conserved essential residues, comprise the substrate-binding pocket, the extrafacial gate, and the intrafacial gate (Xuan et al. 2013; Tao et al. 2015). The orthologous SWEET1 in Camellia sinensis (tea) transports glucose, glucose analogues, and other hexoses (Wang et al. 2018).
Sweet1 of Arabidopsis thalinana (Q8L9J7)
The 7 TMS (242aa) bacterial MtN3 homologue
MtN3 homologue of Mycoplasma arthritidis (B3PMT4)
SWEET homologue of 125 aas and 3 TMSs; resembles 2.A.123.2.3 with all 3 TMSs overlapping.
SWEET homologue of Phytophthora sojae (Soybean stem and root rot agent) (Phytophthora megasperma f. sp. glycines)
SWEET homologue of 125 aas and 3 TMSs. Closely related to 2.A.123.2.10.
SWEET homologue of Phytophthora parasitica
SWEET homologue of 84 aas and 3 TMSs
SWEET homologue of Methanocella conradii
Uncharacterized protein of 728 aas and 5 putative TMSs with 4 N-terminal TMSs, where the first 3 are homologous to semisweets of 3 TMSs. The long sequence with one large centrally located peak of hydrophobicity includes several recognized protein domains following the SWEET domain in the following order: Cache-3 - Cache-1 - dimerization interface domain - HAMP domain - followed by two PAS domains. Another protein (UniProt acc #I3IJJ5 of 762 aas), has residues 3 - 635 aas) showing 83% sequence identity with residues 96 - 728 in 2.A.123.2.13.
UP of Candidatus Jettenia caeni
SemiSWEET of 86 aas and 3 TMSs specific for sucrose. The basic unit of SWEETs may be a 3-TMS unit, and it has been suggested that a functional transporter contains at least four such domains, although this suggestion has not been substantiated (Xuan et al. 2013).
SemiSWEET of Bradyrhizobium diazoefficiens
Putative uncharacterized protein of 99 aas and 3 TMSs
Hypothetical protein UW38 of Candidatus Saccharibacteria bacterium
Facilitated glucose/sucrose/sugar/monoolein transporter of 89 aas and 3 TMSs. The homodimer mediates transmembrane sugar transport down a concentration gradient. Transport is probably effected by rocking-type movements, where a cargo-binding cavity opens first on one and then on the other side of the membrane (Lee et al. 2015).
Semisweet sugar transporter of E. coli
3 TMS MtN3 homologue (85aas)
MtN3 of MtN3 of Prochlorococcus marinus (A2BS89)
Half sized (3 TMS) bacterial MtN3 protein homologue (85aas)
MtN3 homologue of Fusobacterium mortiferum (C3WG44)
3 TMS bacterial MtN3 homologue (96aas)
MtN3 homologue of Leptospira interrogans (Q8F4F7)
3 TMS Sweet homologue, MJ_0110 (93aas)
MJ_0110 of Methanocaldococcus jannashii (Q57574)
SemiSWEET half glucose transporter of 93 aas and 3 TMSs with an N-terminal amphipathic α-helix. The protein occurs as a tight homodimer with the translocation channel between the two monomers. The 3-d structure is known at 2.4 Å resolution revealing the outward open conformation (Xu et al. 2014). The occluded state of the Vibrio sp. N418 SemiSWEET (9.A.58.3.1) has been solved at 1.7 Å resolution (Xu et al. 2014). The presence of these two states argues in favor of a carrier (rocker switch) mechanism rather than a channel-type mechanism (Xu et al. 2014).
SemiSWEET of Leptospira biflexa
SemiSWEET homologue of 89 aas and 3 TMSs
SemiSWEET of Rickettsia bellii
SWEET homologue of 141 aas and 4 putative TMSs.
SWEET homologue of Anabaena variabilis
SWEET homologue of 231 aas and 7 TMSs
SWEET homologue of Mycoplasma hyopneumoniae
SemiSWEET half putative sugar transporter of 97 aas and 3 TMSs with an N-terminal amphipathic α-helix. The protein occurs as a tight homodimer with the translocation channel between the two monomers. The 3-d structure is known at 1.7 Å resolution revealing the occluded conformation (Xu et al. 2014). The outward open state of the Leptospira biflexa SemiSWEET (2.a.123.2.6) has been solved at 2.4 Å resolution (Xu et al. 2014). The presence of these two states argues in favor of a carrier (rocker switch) mechanism rather than a channel-type mechanism (Xu et al. 2014).
SemiSWEET of Vibrio sp. N418
Uncharacterized protein of 107 aas.
UP of Rhodobacteraceae bacterium KLH11
Uncharacterized conserved protein of 273 aas and 7 TMSs containing PQ loop repeats.
UP of Geodermatophilus obscurus
Uncharacterized protein of 97 aas and 3 TMSs.
UP of Photobacterium leiognathi
Membrane protein of 209 aas and 7 TMSs with a putative N-terminal lipid A disaccharide synthase domain. This protein is a member of the "Lipid A Biosynthesis, N-terminal (LAB_N) domain in Pfam/CDD, related to the SWEET family.
Membrane protein of Gramella forsetii
Uncharacterized protein of 115 aas and 3 TMSs.
UP of Frateuria aurantia (Acetobacter aurantius)
Uncharacterized protein (putative lipid A synthesis protein domain) of 115 aas and 3 TMSs.
UP of Stenotrophomonas maltophilia (Pseudomonas maltophilia) (Xanthomonas maltophilia)
Uncharacterized protein of 208 aas and 2 N-terminal TMSs.
UP of Balneolaceae bacterium (soda lake metagenome)
Uncharacterized protein of 207 aas and 2 or 3 N-terminal TMSs
UP of Serinicoccus sediminis
Uncharacterized protein of 204 aas and 3 N-terminal TMSs followed by a large hydrophilic domain, characteristic of this subfamily (TC# 2.A.123.5).
UP of Janibacter terrae (hydrocarbon metagenome)
Uncharacterized protein of 210 aas and 3 N-terminal TMSs.
UP of Chitinophagaceae bacterium (ecological metagenome)
Uncharacterized protein of 207 aas and 3 or more TMSs
UP of Methanohalobium evestigatum